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Alkylated and methylene ketones are versatile synthetic intermediates useful in the manufacture of many chemicals that exhibit pharmaceutical, herbicidal and other activities. For example, methylisopropylketone (Me.sub.2 CHCOMe) is used to prepare the pesticide, 2,2-dimethyl-3-(2-halovinyl)cyclopropanecarboxylic acid esters and the antimycotic agents substituted 1,3-diazolyl-2-propanols while desoxyanisoin is used to prepare 4,5-bis(p-methoxyphenyl)-1,2,3-thiadiazole which exhibit activity as an inhibitor of collagen-induced aggregation of human platelet-rich plasma.
Heretofore, the two most commonly employed reagent combinations for dehydroxylation of alpha-hydroxyketones are red phosphorus/iodine and trimethylsilyliodide/sodium thiosulfate. Because of the versatility as synthetic intermediates of these dehydroxylated alpha-hydroxyketones, it would be advantageous to have other methods for preparing these compounds in good yields. It would be even more advantageous to have facile access to alpha-methylene ketones and alpha-alkylated ketones of the type R.sub.1 C(O)CH.sub.2 R.sub.2 and R.sub.1 C(O)CHR.sub.2 R.sub.3, respectively, by reduction of the corresponding alpha-hydroxyketones because these alpha-hydroxyketones are available in good yields by chlorotrimethylsilyl-mediated acyloin condensations of the appropriate esters. Further, the use of a readily available phosphorus derived reagent to accomplish this transformation would be advantageous.
Lithium diphenylphosphide (LDP) has been used as a reagent for the epoxide-mediated inversion of olefin stereochemistry. This reaction proceeds via stereospecific epoxide ring opening by LDP. The intermediate formed is treated with methyliodide effecting quaternization of phosphorus to give a betaine. Subsequent fragmentation of the betaine, usually at room temperature, produces an olefin and methyldiphenylphosphine oxide. This methodology has been employed to isomerize a variety of olefins via their epoxide derivatives, most notably, the conversion of cis- to trans-cyclooctene in greater than 90% yield with greater than 99.5% isomeric purity (see Phosphorus Betaines Derived from Cycloheptane and Cyclooctene Oxides, Inversion of Cyclooctenes, Vedejs, E.; Snoble, K. A. J.; Fuchs, P. L., J. Org. Chem. 1973, 38, 1178-1183).